Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells

0523649 - ÚEB 2020 RIV FR eng J - Journal Article
Jorda, Radek - Magar, P. P. - Hendrychová, Denisa - Pauk, K. - Dibus, M. - Pilařová, E. - Imramovský, A. - Kryštof, Vladimír
Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells.
European Journal of Medicinal Chemistry. Roč. 188, FEB 15 (2020), č. článku 112036. ISSN 0223-5234. E-ISSN 1768-3254
Institutional support: RVO:61389030
Keywords : Adhesion * Apoptosis * cytotoxicity * Detachment * Dipeptide
OECD category: Medicinal chemistry
Impact factor: 6.514, year: 2020
Method of publishing: Open access
http://doi.org/10.1016/j.ejmech.2020.112036

Here, we describe the synthesis and biological characterization of 32 novel phenylalanine and leucine dipeptides modified on both the N and C termini by salicylic acid and aromatic or alicyclic amines, respectively. All compounds displayed antiproliferative activity in the tested cancer cell lines and eight of the compounds exhibited single digit micromolar GI50 values. Treated cells rapidly detached from surface of tissue culture dishes and we found that focal adhesion kinase (FAK), p130CAS and paxillin, which are important regulators of cell adhesion, were dephosphorylated at Y397, Y410 and Y118, respectively. The most potent compound reduced proliferation in the HCT-116 cell line in a dose-dependent manner, as shown by a decrease in 5-bromo-2′-deoxyuridine incorporation into DNA. Furthermore, this compound increased the levels of several apoptotic markers, including activated caspases, and increased site-specific poly-(ADP-ribose)polymerase (PARP) cleavage.
Permanent Link: http://hdl.handle.net/11104/0307967